Investigation will continue concerning an experimental model of protease inhibitor (PI) deficiency. In man the importance of heterozygous levels of PI deficiency in the pathogenesis of emphysema is uncertain. Our studies will utilize specific metabolic inhibitors which perturb hepatic glycoprotein synthesis and secretion to alter plasma PI. These drugs include galactosamine cycloheximide, colchicine and arabinofuranosyl cytosine and puromycin. These agents will be analyze in vitro in a liver perfusion system and after chronic in vivo administration. The effects of these agents on hepatic glycoprotein synthesis on hepatic and circulating protease inhibitors, and/or selected hepatic enzymes will be evaluated and correlated with light and TEM microscopy of the hepatic parenchymal cells. We will also study the effects of ac-ala-ala-pro-ala chloromethylketone and the ac-ala-ala-pro-val chloromethylketone (synthetic elastase inhibitors) to evaluate tissue distribution ability to penetrate leucocytes and the effects on leucocyte and macrophage elastases. The effect of depression of the native hepatically generated PI on the course of a standardized lung injury induced by elastase will be evaluated to determine the rate of PI in the genesis of experimental emphysema. In a like manner, the effect of the peptide chloromethyl ketones on experimental emphysema will be studied.